Walcheck B, Jutila M A
Montana State University, Bozeman 59717.
Int Immunol. 1994 Jan;6(1):81-91. doi: 10.1093/intimm/6.1.81.
Lymphocyte migration from the blood into specific tissues is directed by their expression of adhesion molecules referred to as homing receptors. The homing receptor L-selectin, for example, directs the migration of lymphocytes into peripheral lymph nodes (PLN). Since bovine gamma delta T cells, a major lymphocyte subset in peripheral blood (25-50%), represent only a minor subset in PLN, we examined whether these cells lack expression or function of L-selectin. We found that bovine gamma delta T cells expressed L-selectin at levels higher (2- to 5-fold) than alpha beta T cells and B cells. Furthermore, gamma delta T cells accumulated along the vascular wall of venules that support lymphocyte extravasation into PLN (MECA-79+ venules) in vivo and bound mouse PLN high endothelial cell venules in an ex vivo binding assay. In contrast to this primary adhesive event, we directly demonstrate that gamma delta T cells in vivo do not appreciably extravasate from the blood into the parenchyma of lymph nodes. Since the lack of functional L-selectin expression could not account for the inability of gamma delta T cells to enter PLN, we tested for other differences between gamma delta T cells and PLN homing lymphocytes related to the processes following primary adhesion; for instance, the down-regulation of L-selectin expression following short-term activation and the expression of accessory adhesion molecules necessary for transendothelial migration. We found that gamma delta and alpha beta T cells demonstrate differential down-regulation of L-selectin after PMA activation. Kinetic analysis revealed that, at all time points after PMA treatment, L-selectin expression remained significantly higher on gamma delta T cells and was down-regulated at a slower rate compared with alpha beta T cells. However, the expression levels of CD44 and CD18 on gamma delta and alpha beta T cells were found to be equivalent. This study is the first to demonstrate for lymphocytes that the expression of L-selectin alone does not predict a PLN homing capacity. Our results suggest that the gamma delta T cells' reduced ability to enter PLN may be due to inefficient down-regulation of L-selectin compared with non-gamma delta lymphocytes, thus potentially disrupting the dynamics of the extravasation event.
淋巴细胞从血液迁移到特定组织是由它们表达的被称为归巢受体的黏附分子所引导的。例如，归巢受体L-选择素引导淋巴细胞迁移到外周淋巴结（PLN）。由于牛γδT细胞是外周血中的主要淋巴细胞亚群（占25%-50%），但在PLN中仅占次要亚群，我们研究了这些细胞是否缺乏L-选择素的表达或功能。我们发现牛γδT细胞表达L-选择素的水平高于αβT细胞和B细胞（高2至5倍）。此外，γδT细胞在体内沿着支持淋巴细胞外渗到PLN的小静脉血管壁聚集（MECA-79+小静脉），并且在体外结合试验中与小鼠PLN高内皮细胞小静脉结合。与这一初始黏附事件形成对比的是，我们直接证明体内的γδT细胞不会明显地从血液外渗到淋巴结实质中。由于缺乏功能性L-选择素表达不能解释γδT细胞无法进入PLN的原因，我们测试了γδT细胞与PLN归巢淋巴细胞在初始黏附后相关过程中的其他差异；例如，短期激活后L-选择素表达的下调以及跨内皮迁移所需的辅助黏附分子的表达。我们发现γδT细胞和αβT细胞在佛波酯（PMA）激活后L-选择素的下调存在差异。动力学分析显示，在PMA处理后的所有时间点，γδT细胞上L-选择素的表达仍然显著高于αβT细胞，并且与αβT细胞相比下调速度较慢。然而，发现γδT细胞和αβT细胞上CD44和CD18的表达水平相当。这项研究首次证明，对于淋巴细胞而言，仅L-选择素的表达并不能预测其PLN归巢能力。我们的结果表明，γδT细胞进入PLN的能力降低可能是由于与非γδ淋巴细胞相比，L-选择素的下调效率低下，从而可能破坏了外渗事件的动态过程。
